Emerging roles of metabolite-derived posttranslational modifications in vascular smooth muscle cell phenotypic state and fate

The interaction between metabolic reprogramming and key signaling pathways is required for vascular smooth muscle cells (VSMCs) phenotypic transitions and the development of disease. In response to pathological stimuli, VSMCs experience metabolic reprogramming to meet their increased energy demands and biomass synthesis. Metabolite-derived post translational modifications (PTMs) act as a key player in linking metabolic reprogramming to the VSMC phenotypic transitions. The alteration of metabolites of glucose, lipids and amino acids in the microenvironment also governs key signaling pathways via PTMs in VSMCs. Here, we introduce the basic processes of metabolite-derived PTMs, including phosphorylation, succinylation, acetylation, lactylation, O-GlcNAcylation, palmitoylation, crotonylation, methylation, serotonylation and glutamylation, emphasize the importance of cross talk of PTMs and summarize the underlying mechanisms of metabolite-derived PTMs in regulating the VSMC phenotypic transitions.